Full Text Journal Articles by
Author Sergey N Savinov

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Identification of Protein Recognition Elements within Heparin Chains Using Enzymatic Foot-Printing in Solution and Online SEC/MS.

Chendi Niu, Yunlong Zhao, Cedric E Bobst, Sergey N Savinov, Igor A Kaltashov,

Understanding molecular mechanisms governing interactions of glycosaminoglycans (such as heparin) with proteins remains challenging due to their enormous structural heterogeneity. Commonly accepted approaches seek to reduce the structural complexity by searching for "binding epitopes" within the limited subsets of short heparin oligomers produced either enzymatically or synthetically. A top-down approach ... Read more >>

Anal. Chem. (Analytical chemistry)
[2020, 92(11):7565-7573]

Cited: 1 time

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Synthesis of C-Ring-Substituted Vasicinones and Luotonins via Regioselective Aza-Nazarov Cyclization of Quinazolinonyl Enones.

Sivappa Rasapalli, Vamshikrishna Reddy Sammeta, Zachary F Murphy, Yanchang Huang, Jeffrey A Boerth, James A Golen, Sergey N Savinov,

A facile synthesis of C-ring substituted luotonins and vasicinones has been realized via a super-acid-mediated aza-Nazarov cyclization of quinazolinonyl enones. The regioselectivity of the cyclization is highly dependent on proton availability in the reaction medium. ... Read more >>

Org. Lett. (Organic letters)
[2019, 21(24):9824-9828]

Cited: 0 times

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Drug Screening for Discovery of Broad-spectrum Agents for Soil-transmitted Nematodes.

Mostafa A Elfawal, Sergey N Savinov, Raffi V Aroian,

Soil-transmitted nematodes (STNs), namely hookworms, whipworms, and ascarids, are extremely common parasites, infecting 1-2 billion of the poorest people worldwide. Two benzimidazoles, albendazole and mebendazole, are currently used in STN mass drug administration, with many instances of low/reduced activity reported. New drugs against STNs are urgently needed. We tested various ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):12347]

Cited: 2 times

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Modulation of Amyloid-β42 Conformation by Small Molecules Through Nonspecific Binding.

Chungwen Liang, Sergey N Savinov, Jasna Fejzo, Stephen J Eyles, Jianhan Chen,

Aggregation of amyloid-β (Aβ) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and scyllo-inositol, which are AD drug candidates currently under ... Read more >>

J Chem Theory Comput (Journal of chemical theory and computation)
[2019, 15(10):5169-5174]

Cited: 3 times

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Mutations in TTC29, Encoding an Evolutionarily Conserved Axonemal Protein, Result in Asthenozoospermia and Male Infertility.

Patrick Lorès, Denis Dacheux, Zine-Eddine Kherraf, Jean-Fabrice Nsota Mbango, Charles Coutton, Laurence Stouvenel, Come Ialy-Radio, Amir Amiri-Yekta, Marjorie Whitfield, Alain Schmitt, Caroline Cazin, Maëlle Givelet, Lucile Ferreux, Selima Fourati Ben Mustapha, Lazhar Halouani, Ouafi Marrakchi, Abbas Daneshipour, Elma El Khouri, Marcio Do Cruzeiro, Maryline Favier, François Guillonneau, Marhaba Chaudhry, Zeinab Sakheli, Jean-Philippe Wolf, Catherine Patrat, Gérard Gacon, Sergey N Savinov, Seyedeh Hanieh Hosseini, Derrick R Robinson, Raoudha Zouari, Ahmed Ziyyat, Christophe Arnoult, Emmanuel Dulioust, Mélanie Bonhivers, Pierre F Ray, Aminata Touré,

In humans, structural or functional defects of the sperm flagellum induce asthenozoospermia, which accounts for the main sperm defect encountered in infertile men. Herein we focused on morphological abnormalities of the sperm flagellum (MMAF), a phenotype also termed "short tails," which constitutes one of the most severe sperm morphological defects ... Read more >>

Am. J. Hum. Genet. (American journal of human genetics)
[2019, 105(6):1148-1167]

Cited: 0 times

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Ruthenium coordination preferences in imidazole-containing systems revealed by electrospray ionization mass spectrometry and molecular modeling: Possible cues for the surprising stability of the Ru (III)/tris (hydroxymethyl)-aminomethane/imidazole complexes.

Igor A Kaltashov, Anton El Khoury, Chengfeng Ren, Sergey N Savinov,

Ruthenium is a platinoid that exhibits a range of unique chemical properties in solution, which are exploited in a variety of applications, including luminescent probes, anticancer therapies, and artificial photosynthesis. This paper focuses on a recently demonstrated ability of this metal in its +3 oxidation state to form highly stable ... Read more >>

J Mass Spectrom (Journal of mass spectrometry : JMS)
[2020, 55(2):e4435]

Cited: 0 times

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Chemoproteomics Using Nucleotide Acyl Phosphates Reveals an ATP Binding Site at the Dimer Interface of Procaspase-6.

Eric S Okerberg, Kevin B Dagbay, Jennifer L Green, Ishankumar Soni, Arwin Aban, Tyzoon K Nomanbhoy, Sergey N Savinov, Jeanne A Hardy, John W Kozarich,

Acyl phosphates of ATP (ATPAc) and related nucleotides have proven to be useful for the interrogation of known nucleotide binding sites via specific acylation of conserved lysines (K). In addition, occasional K acylations are identified in proteins without such known sites. Here we present a robust and specific acylation of ... Read more >>

Biochemistry (Biochemistry)
[2019, 58(52):5320-5328]

Cited: 1 time

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Corrigendum: Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.

Patrick Lorès, Charles Coutton, Elma El Khouri, Laurence Stouvenel, Maëlle Givelet, Lucie Thomas, Baptiste Rode, Alain Schmitt, Bruno Louis, Zeinab Sakheli, Marhaba Chaudhry, Angeles Fernandez-Gonzales, Alex Mitsialis, Denis Dacheux, Jean-Philippe Wolf, Jean-François Papon, Gérard Gacon, Estelle Escudier, Christophe Arnoult, Mélanie Bonhivers, Sergey N Savinov, Serge Amselem, Pierre F Ray, Emmanuel Dulioust, Aminata Touré,

Hum. Mol. Genet. (Human molecular genetics)
[2019, 28(6):1052]

Cited: 1 time

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Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.

Patrick Lorès, Charles Coutton, Elma El Khouri, Laurence Stouvenel, Maëlle Givelet, Lucie Thomas, Baptiste Rode, Alain Schmitt, Bruno Louis, Zeinab Sakheli, Marhaba Chaudhry, Angeles Fernandez-Gonzales, Alex Mitsialis, Denis Dacheux, Jean-Philippe Wolf, Jean-François Papon, Gérard Gacon, Estelle Escudier, Christophe Arnoult, Mélanie Bonhivers, Sergey N Savinov, Serge Amselem, Pierre F Ray, Emmanuel Dulioust, Aminata Touré,

Motile cilia and sperm flagella share an extremely conserved microtubule-based cytoskeleton, called the axoneme, which sustains beating and motility of both organelles. Ultra-structural and/or functional defects of this axoneme are well-known to cause primary ciliary dyskinesia (PCD), a disorder characterized by recurrent respiratory tract infections, chronic otitis media, situs inversus, ... Read more >>

Hum. Mol. Genet. (Human molecular genetics)
[2018, 27(7):1196-1211]

Cited: 11 times

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Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.

Agne Tubeleviciute-Aydin, Libin Zhou, Gyanesh Sharma, Ishankumar V Soni, Sergey N Savinov, Jeanne A Hardy, Andrea C LeBlanc,

The cysteine protease Caspase-6 (Casp6) is a potential therapeutic target of Alzheimer Disease (AD) and age-dependent cognitive impairment. To assess if Casp6 is essential to human health, we investigated the effect of CASP6 variants sequenced from healthy humans on Casp6 activity. Here, we report the effects of two rare Casp6 ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):4428]

Cited: 2 times

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Interaction of Cholesterol with Perfringolysin O: What Have We Learned from Functional Analysis?

Sergey N Savinov, Alejandro P Heuck,

Cholesterol-dependent cytolysins (CDCs) constitute a family of pore-forming toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores by inserting a large β-barrel into cholesterol-containing membranes. Cholesterol is absolutely required for pore-formation. For most CDCs, binding to cholesterol triggers conformational changes that lead to oligomerization and end in pore-formation. Perfringolysin ... Read more >>

Toxins (Basel) (Toxins)
[2017, 9(12):]

Cited: 6 times

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Interactions of Haptoglobin with Monomeric Globin Species: Insights from Molecular Modeling and Native Electrospray Ionization Mass Spectrometry.

Ololade Fatunmbi, Rinat R Abzalimov, Sergey N Savinov, Anne Gershenson, Igor A Kaltashov,

Haptoglobin (Hp) binds free hemoglobin (Hb) dimers to prevent negative consequences of Hb circulation in the extracellular environment. Although both monomeric Hb and myoglobin (Mb) species also present potential risks, their interactions with Hp have not been extensively studied. Mb is homologous to both the α- and β-chains of Hb ... Read more >>

Biochemistry (Biochemistry)
[2016, 55(12):1918-1928]

Cited: 2 times

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Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP.

Jessica Escoffier, Hoi Chang Lee, Sandra Yassine, Raoudha Zouari, Guillaume Martinez, Thomas Karaouzène, Charles Coutton, Zine-Eddine Kherraf, Lazhar Halouani, Chema Triki, Serge Nef, Nicolas Thierry-Mieg, Sergey N Savinov, Rafael Fissore, Pierre F Ray, Christophe Arnoult,

In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage of embryo development. Ca(2+) signaling is elicited by the delivery of an oocyte-activating factor by the sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as the likely candidate to ... Read more >>

Hum. Mol. Genet. (Human molecular genetics)
[2016, 25(5):878-891]

Cited: 19 times

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Evaluation of AaDOP2 receptor antagonists reveals antidepressants and antipsychotics as novel lead molecules for control of the yellow fever mosquito, Aedes aegypti.

Jason M Conley, Jason M Meyer, Andrew B Nuss, Trevor B Doyle, Sergey N Savinov, Catherine A Hill, Val J Watts,

The yellow fever mosquito, Aedes aegypti, vectors disease-causing agents that adversely affect human health, most notably the viruses causing dengue and yellow fever. The efficacy of current mosquito control programs is challenged by the emergence of insecticide-resistant mosquito populations, suggesting an urgent need for the development of chemical insecticides with ... Read more >>

J. Pharmacol. Exp. Ther. (The Journal of pharmacology and experimental therapeutics)
[2015, 352(1):53-60]

Cited: 3 times

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The Cdk/cDc14 module controls activation of the Yen1 holliday junction resolvase to promote genome stability.

Christie L Eissler, Gerard Mazón, Brendan L Powers, Sergey N Savinov, Lorraine S Symington, Mark C Hall,

Faithful genome transmission during cell division requires precise, coordinated action of DNA metabolic enzymes, including proteins responsible for DNA damage detection and repair. Dynamic phosphorylation plays an important role in controlling repair enzymes during the DNA damage response (DDR). Cdc14 phosphatases oppose cyclin-dependent kinase (Cdk) phosphorylation and have been implicated ... Read more >>

Mol. Cell (Molecular cell)
[2014, 54(1):80-93]

Cited: 50 times

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Chemical and biological mechanisms of phytochemical activation of Nrf2 and importance in disease prevention.

Aimee L Eggler, Sergey N Savinov,

Plants are an incredibly rich source of compounds that activate the Nrf2 transcription factor, leading to upregulation of a battery of cytoprotective genes. This perspective surveys established and proposed molecular mechanisms of Nrf2 activation by phytochemicals with a special emphasis on a common chemical property of Nrf2 activators: the ability ... Read more >>

Recent Adv Phytochem (Recent advances in phytochemistry)
[2013, 43:121-155]

Cited: 5 times

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Intracellular detection and evolution of site-specific proteases using a genetic selection system.

Kathryn D Verhoeven, Olvia C Altstadt, Sergey N Savinov,

Development of endoproteases, programmed to promote degradation of peptides or proteins responsible for pathogenic states, represents an attractive therapeutic strategy, since such biocatalytic agents could be directed against a potentially unlimited repertoire of extracellular proteinaceous targets. Difficulties associated with engineering enzymes with tailor-made substrate specificities have, however, hindered the discovery ... Read more >>

Appl. Biochem. Biotechnol. (Applied biochemistry and biotechnology)
[2012, 166(5):1340-1354]

Cited: 9 times

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Functional profiling of p53-binding sites in Hdm2 and Hdmx using a genetic selection system.

Shreya Datta, Megan E Bucks, Dipankar Koley, Pei Xin Lim, Sergey N Savinov,

Upregulation of structurally homologous oncoproteins Hdm2 and Hdmx has been linked to the depletion or inactivation of their common regulation target the tumor suppressor p53 protein leading to the progression of cancer. The restoration of the p53 function, rendered suppressed or dormant by these negative regulators, establishes, therefore, a unique ... Read more >>

Bioorg. Med. Chem. (Bioorganic & medicinal chemistry)
[2010, 18(16):6099-6108]

Cited: 6 times

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Direct evaluation of cellular internalization rates using chromogenic disulfides.

Megan E Bucks, Sergey N Savinov,

A practical assay, which exploits the maintenance of the cytoplasmic redox balance in live cells, has been developed to report in real time on relative cellular internalization rates of molecules derivatized as chromogenic disulfides. ... Read more >>

Mol Biosyst (Molecular bioSystems)
[2010, 6(7):1176-1179]

Cited: 0 times

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Chemoselective nitration of phenols with tert-butyl nitrite in solution and on solid support.

Dipankar Koley, Olvia C Colón, Sergey N Savinov,

tert-Butyl nitrite was identified as a safe and chemoselective nitrating agent that provides preferentially mononitro derivatives of phenolic substrates in the presence of potentially competitive functional groups. On the basis of our control experiments, we propose that the reaction proceeds through the formation of O-nitrosyl intermediates prior to C-nitration via ... Read more >>

Org. Lett. (Organic letters)
[2009, 11(18):4172-4175]

Cited: 25 times

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Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus.

Hui Xie, Danny Ng, Sergey N Savinov, Barna Dey, Peter D Kwong, Richard Wyatt, Amos B Smith, Wayne A Hendrickson,

The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2007, 50(20):4898-4908]

Cited: 24 times

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Engineering an affinity tag for genetically encoded cyclic peptides.

Todd A Naumann, Sergey N Savinov, Stephen J Benkovic,

Peptide expression libraries are valuable probes of cellular function. SICLOPPS technology merges the principal advantages of both genetic methods and small-molecule approaches in yielding superior library sizes of operationally stable, structurally well-defined entities with an established biological and medicinal record. Here, we describe development, application, and the first-generation library implementation ... Read more >>

Biotechnol. Bioeng. (Biotechnology and bioengineering)
[2005, 92(7):820-830]

Cited: 12 times

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Investigation of an antibody-ligase. Evidence for strain-induced catalysis.

Sergey N Savinov, Ralph Hirschmann, Stephen J Benkovic, Amos B Smith,

Catalytic antibody 16G3, a peptide ligase with extended substrate scope has been characterized mechanistically exploiting a set of systematically designed perspective substrates 6-9, two of which, thioesters 8 and 9 act instead as inhibitors. Taken together the structure/activity relationships suggest a catalytic mechanism dependent on induction of strain, programmed via ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2003, 13(7):1321-1324]

Cited: 1 time

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Peptide-small molecule hybrids via orthogonal deprotection-chemoselective conjugation to cysteine-anchored scaffolds. A model study.

Amos B Smith, Sergey N Savinov, Uma V Manjappara, Irwin M Chaiken,

The feasibility of an orthogonal deprotection-conjugation protocol, holding the promise of libraries of functionally diverse chemical probes attached to cysteine-anchored peptide scaffolds, has been explored with a model system. The necessary tools for assembly of the hybrid libraries have been prepared and the tandem procedure optimized. S-alkylation and S-sulfenylation are ... Read more >>

Org. Lett. (Organic letters)
[2002, 4(23):4041-4044]

Cited: 18 times

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Diastereofacial solid phase synthesis and self-promoted cleavage of a [2.2.1] bicyclic diversity scaffold.

Sergey N Savinov, David J Austin,

[reaction: see text]. We have previously described a diastereofacially selective 1,3-dipolar cycloaddition reaction of isomünchnones with vinyl ethers. While adapting this methodology for solid phase synthesis, we discovered a chemoselective and self-promoted linker aminolysis that provides liberated product in high purity, at a significantly enhanced rate. Herein we describe the ... Read more >>

Org. Lett. (Organic letters)
[2002, 4(9):1419-1422]

Cited: 3 times

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